Structured Abstract

Context:

Epidemiologic studies and clinical trials have reported
beneficial effects of fish consumption on several cardiovascular disease (CVD)
outcomes, such as all cause mortally, CVD death, cardiac death, sudden death,
myocardial infarction and stroke. However, the mechanisms of this benefit are
unclear.

Objectives:

As the first of a 3-part report on this topic, we analyzed
relevant nutrition databases to describe the intake levels of various omega-3 fatty
acids in the US population. We also performed a systematic review of the literature
to assess the benefits of omega-3 fatty acid supplements or fish consumption on
various CVD outcomes and to assess adverse events associated with intake of omega-3
fatty acid supplements.

Data Sources:

The Continuing Survey of Food Intakes by Individuals
(CSFII) was reviewed and the third National Health and Nutrition Examination Survey
(NHANES III) was analyzed for dietary intake. Medline, Embase, Cochrane Central
Register of Controlled Trials, Biological Abstracts, and Commonwealth Agricultural
Bureau databases were searched for potentially relevant studies to address the
questions on the effects of omega-3 fatty acids.

Study Selection:

We screened over 7,464 abstracts and retrieved 768
full text articles. Thirty-nine studies met our inclusion criteria and provided data
to address the key questions in this report. We used randomized controlled trials
(RCTs) and observational studies that quantified the amount of fish or omega-3 fatty
acid intake and that were at least 1 year in duration to assess the effects of
omega-3 fatty acid consumption on CVD outcomes on risk of CVD in the general
population (those without known CVD) and in populations at high risk due to
pre-existing CVD or multiple CVD risk factors.

Data Extraction:

From each study that qualified, we extracted
information about the study design, population demographics, the prescribed or
estimated amount of omega-3 fatty acid supplements or fish consumed, and outcomes.
For RCTs, we extracted information about the randomization and blinding techniques
to assess methodological quality. For prospective cohort studies, we extracted
estimated quantities of fish or fish oil consumed and their associated effect.

Data Synthesis:

The intake of omega-3 fatty acids in the population
varies. Corrected for energy intake, men consume significantly less alpha-linolenic
acid (ALA, 18:3 n-3) than women, adults more than youths, and subjects with a
history of CVD less than those without CVD. Based on analyses of a single 24-hour
dietary recall in NHANES III, only 25% of the US population reported any amount of
daily eicosapentaenoic acid (EPA, 20:5 n-3) or docosahexaenoic acid (DHA, 22:6 n-3)
intake.

Eleven RCTs and 1 prospective cohort study reported outcomes on CVD populations. The
largest trial reported that fish oil (EPA + DHA) reduces all cause mortality and CVD
events, although fish oil has no effect on stroke. Most other studies evaluating
either fish oil or ALA supplements reported similar findings. There were few trials
of ALA. In the only RCT that directly compared ALA and fish oil, both treatments
were efficacious in reducing CVD outcome. No significant difference was found
between the 2 supplements.

Twenty-two prospective cohort studies and 1 RCT reported data on general populations.
Among the cohort studies there were considerable differences among the populations
studied, as well as in the estimates of fish or omega-3 fatty acids consumed. Most
of the large cohort studies found fish consumption was associated with lower rates
of all cause mortality and CVD outcomes, but several studies reported no significant
or negative results for the CVD outcomes. A significant benefit for stroke was
reported in 1 study. The single RCT which evaluated ALA in a large general
population lasted only 1 year yielding no significant results. Gastrointestinal
symptoms associated with fish oil or ALA supplements are the most commonly reported
adverse event and may require dose reduction or discontinuation in some individuals.
Clinical bleeding is a theoretical concern but this was not borne out by the
evidence.

Conclusions:

Overall, consumption of omega-3 fatty acids from fish or
from supplements of fish oil reduces all cause mortality and various CVD outcomes.
The evidence for ALA supplements is sparse and inconclusive. The adverse events due
to consumption of fish oil or ALA supplements appear to be minor. Many questions
remain. The studies were heterogeneous with regard to the methods of estimating fish
or omega-3 fatty acid intake, background diets, settings, and the methods of
reporting results. Due to these reasons, the validity of applying the results of
studies conducted in countries outside of the US to the US population is uncertain.
The optimal quantity and type of omega-3 fatty acid, and the optimal ratio of
omega-3 to omega-6 fatty acid (if such an optimal ratio exists), remain undefined.
Not much data exists concerning the needs of different subpopulations. Different
types of fish and the method of food preparation may have different effects. Future
research needs to address these issues.

This report may be used, in whole or in part, as the basis for development of
clinical practice guidelines and other quality enhancement tools, or a basis for
reimbursement and coverage policies. AHRQ or U.S. Department of Health and Human
Services endorsement of such derivative products may not be stated or implied.

AHRQ is the lead Federal agency charged with supporting research designed to improve
the quality of health care, reduce its cost, address patient safety and medical
errors, and broaden access to essential services. AHRQ sponsors and conducts
research that provides evidence-based information on health care outcomes; quality;
and cost, use, and access. The information helps health care decisionmakers—patients
and clinicians, health system leaders, and policymakers—make more informed decisions
and improve the quality of health care services.

The authors of this report are responsible for its content. Statements in the report
should not be construed as endorsement by the Agency for Healthcare Research and
Quality or the U.S. Department of Health and Human Services of a particular drug,
device, test, treatment, or other clinical service.